Regression Modeling of Individual-Patient Correlated Discrete Outcomes with Applications to Cancer Pain Ratings

Abstract

Purpose: To formulate and demonstrate methods for regression modeling of pr obabilities and dispersions for individual-patient longitudinal outcom es taking on discrete numeric values. Methods: Three alternatives for modeling of outcome probabilities are considered. Multinomial probabilities are based on different intercepts and slopes for probabilities of different outcome values. Ordinal probabilities are based on different intercepts and the same slope for probabilities of different outcome values. Censored Poisson probabilities are based on the same intercept and slope for probabilities of different outcome values. Parameters are estimated with extended linear mixed modeling maximizing a likelihood-like function based on the multivariate normal density that accounts for within-patient correlation. Formulas are provided for gradient vectors and Hessian matrices for estimating model parameters. The likelihood-like function is also used to compute cross-validation scores for alternative models and to control an adaptive modeling process for identifying possibly nonlinear functional relationships in predictors for probabilities and dispersions. Example analyses are provided of daily pain ratings for a cancer patient over a period of 97 days. Results: The censored Poisson approach is preferable for modeling these data, and presumably other data sets of this kind, because it generates a competitive model with fewer parameters in less time than the other two approaches. The generated probabilities for this m odel are distinctly nonlinear in time while the dispersions are distinctly nonconstant over time, demonstrating the need for adaptive modeling of such data. The analyses also address the dependence of these daily pain ratings on ti me and the daily numbers of pain flares. Probabilities and dispersio ns change differently over time for different numbers of pain flares. Conclusions: Adaptive modeling of daily pain ratings for individual cancer patients is an effective way to identify nonlinear relationships in time as well as in other predictors such as the number of pain flares.